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Biomedical subjects

F Yao

Publications and source records attributed to F Yao.

47 records · Page 3Linked to original sources

Association of a major transcriptional regulatory protein, ICP4, of herpes simplex virus type 1 with the plasma membrane of virus-infected cells.

A major transcriptional regulatory protein, ICP4, of herpes simplex virus type 1 (HSV-1) is localized primarily within the nucleus soon after its synthesis. Recent studies have shown that approximately 100 to 200 molecules of ICP4 are located in the tegument region of purified virions (F. Yao and R. J. Courtney, J. Virol. 63:3338-3344, 1989). As an extension to these studies, we present data suggesting that ICP4 may also associate with the plasma membrane of HSV-1-infected cells. The experimental approaches used included the isolation and purification of plasma membranes from HSV-1-infected cells, the isolation of purified vesicular stomatitis virus containing ICP4, and immunofluorescence of HSV-1-infected cells following selective permeabilization with detergent. The results from the above studies support the suggestion that detectable amounts of ICP4 are associated with the inner surface of the plasma membrane of HSV-1-infected cells.

Animals↗

Murine cytotoxic T lymphocytes specific for herpes simplex virus type 1 recognize the immediate early protein ICP4 but not ICP0.

Vaccinia virus recombinants expressing the herpes simplex virus type 1 (HSV-1) genes encoding ICP0 or ICP4 were used to identify the precise target antigen(s) of murine anti-viral cytotoxic T lymphocytes (CTL) specific for the non-structural immediate early proteins. These studies revealed that HSV-1-specific CTL, restricted to class I major histocompatibility complex genes of the H-2k haplotype but not the H-2d or H-2b haplotypes, would lyse autologous cells expressing ICP4. HSV-1-specific CTL derived from various mice strains failed to lyse target cells expressing ICP0. Calculation of the frequencies of H-2k-restricted virus-specific CTL demonstrated that approximately a third of the total HSV-1-specific response was directed against ICP4. Immunization of mice with either recombinant vaccinia virus or transfected L cells expressing ICP4 induced HSV-1-specific lymphoproliferation and delayed hypersensitivity but CTLs were not induced. More importantly, such immunized animals were unable to resist or control a subsequent challenge with virulent HSV-1.

Animals↗

Formulation of malaria treatment policy for children in Côte d'Ivoire as chloroquine resistant Plasmodium falciparum spreads into west Africa.

To develop a malaria treatment policy for children with Plasmodium falciparum, an in vivo and in vitro chloroquine (CQ) sensitivity study was conducted in Côte d'Ivoire in September 1986. The efficacy of a single dose of CQ (10 mg base kg-1, C10) was tested with assessment of subjects on Days 2 and 7 after treatment; 108 (99%) of 109 children were aparasitaemic on Day 7. Of 33 isolates of P. falciparum tested in vitro, two (6%) were resistant to CQ. Although C10 appeared effective clinically and parasitologically in Côte d'Ivoire, a treatment dose of 25 mg of CQ base kg-1 (C25), over three days, was recommended as first-line therapy for malaria. This was because in vivo CQ-resistance will soon spread into other West African countries including Côte d'Ivoire, the C25 dose still retains clinical effectiveness in most partially-immune persons living in areas with low-level chloroquine resistance, and alternate drugs are more expensive.

Animals↗

A major transcriptional regulatory protein (ICP4) of herpes simplex virus type 1 is associated with purified virions.

Herpes simplex virus type 1 was purified by density gradient centrifugation, and the virion-associated proteins were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. By Western blot (immunoblot) analysis with an anti-ICP4 monospecific serum, the results indicated that ICP4, one of the five immediate-early proteins of herpes simplex virus type 1, was associated with the purified virions. To define the location of ICP4 within the virion, trypsin digestion experiments were performed. Purified virions were treated with trypsin in the presence or absence of detergent. The virus envelope appeared to protect ICP4 from the trypsin, since virus-associated ICP4 was sensitive to digestion only after detergent treatment. In addition, ICP4 remained associated with the virus particle when the virion-specific glycoproteins were removed after detergent treatment. Finally, ICP4 was not detected in purified preparations of type A and B capsids isolated from the nuclear fraction of virus-infected cells. The above-mentioned data suggest that detectable amounts of ICP4 are present within the tegument region of the virion.

Animals↗

Colonic adenocarcinoma associated with the acquired immune deficiency syndrome.

Colonic adenocarcinoma developed in an intravenous drug abuser with the acquired immune deficiency syndrome (AIDS) that was diagnosed by the presence of antibodies to the human immunodeficiency virus (HIV), generalized lymphadenopathy, and biopsy proven esophageal candidiasis. The colon cancer presented atypically at a young age with no known risk factors and with a bulky primary tumor and a local fistula. AIDS and AIDS risk factors have been associated with Kaposi's sarcoma, lymphomas, and anal and oropharyngeal carcinoma. This report suggests a possible association between colonic adenocarcinoma and AIDS.

Acquired Immunodeficiency Syndrome↗

Treatment of chronic hepatitis B: new antiviral therapies.

Chronic hepatitis B infection is the most important cause of cirrhosis and hepatocellular carcinoma worldwide. Interferon-alpha has been shown to be effective in approximately one third of patients, and response seems to be sustained in long-term follow-up studies in Western countries. New treatments using lamivudine and other nucleoside analogues such as famciclovir, lobucavir, and adfovir showed promising results although sustained suppression of viral replication is unusual after discontinuation of therapy. The results of recent clinical studies using these nucleoside analogues are discussed in detail in this review. Other important issues such as drug resistance and the role of combination therapy are also addressed.

Drug Therapy, Combination↗

Gene therapy in wound repair and regeneration.

The potential use of gene therapy to treat human disease increases with the development of various physical, chemical, and biological methods to deliver genes to mammalian cells, and with our rapidly expanding knowledge of the human genome. One area of therapeutic interest for gene therapy is the treatment of wound healing disorders. Most recently, recombinant human growth factor therapy has been examined as a means to treat problem wounds. However, this approach suffers from the difficulty in providing an accurate dose of growth factor and the expense of the recombinant proteins. Delivery of a gene that could be expressed within the wound is an attractive alternative to application of the protein. This review discusses several methods that have been used to deliver genes encoding growth factor proteins into wounds and the advantages/disadvantages of each approach. Novel methods to regulate the expression of the transgene are also presented, highlighting the ability of these unique vector systems to adjust gene dose as the wound heals. We expect that gene therapy will become a significant treatment modality for those wound healing pathologies refractory to other wound management approaches in the years ahead.

Genetic Therapy↗

Age and growth factors in porcine full-thickness wound healing.

It has been recognized that the rate of cutaneous wound healing declines with age, yet the molecular processes that affect this decline remain poorly understood. The purpose of this study was to compare reepithelialization and contraction rates, and growth factor profiles in full-thickness wounds in swine of various ages. Multiple full-thickness excisional wounds were created on the dorsum of 24-month-old (n=2), 4-month-old (n=2), and 2-month-old (n=2) Yucatan Minipigs. The extent of reepithelialization was shown to decrease with increasing age in a manner that was statistically significant among the 2-month-old (79%), 4-month-old (48%), and 24-month-old pigs (22%). Enzyme-linked immunosorbent assay results showed that endogenous vascular endothelial growth factor concentrations in the 2- and 4-month-old animals peaked on day 4, reaching levels of 482 pg/ml and 420 pg/ml, respectively. In the 24-month-old pigs the vascular endothelial growth factor concentration peaked later (day 6), and was present at a lower level (229 pg/ml). On day 4 the vascular endothelial growth factor levels in the older pigs reached only 120 pg/ml, representing a four-fold decrease in concentration compared to the younger pigs. A comparison of platelet-derived growth factor-BB concentrations across the age groups showed similar patterns in the 2- and 4-month-old pigs (peaks of 77 and 91 pg/ml on days 2 and 3, respectively), and levels in the 24-month-old were below the sensitivity level (31.5 pg/ml) of the assay. Transforming growth factor-beta1 levels across the age groups did not differ in a manner that was statistically significant, and all age groups peaked on day 9. Wound contraction showed no statistical differences among the age groups from days 3 to 9. On day 11, however, wound contraction in 2-month-old pigs was about 10% faster than in 24-month-old pigs (p < 0.05). These data suggest a possible new algorithm for treating wounds in aged skin, by which exogenous growth factors can be added to the wound microenvironment in doses and at times that match the growth factor profiles observed in wounds made in younger skin.

Age Factors↗